Search Images Maps Play YouTube News Gmail Drive More »
Sign in
Screen reader users: click this link for accessible mode. Accessible mode has the same essential features but works better with your reader.

Patents

  1. Advanced Patent Search
Publication numberUS20030026735 A1
Publication typeApplication
Application numberUS 10/022,670
Publication dateFeb 6, 2003
Filing dateDec 17, 2001
Priority dateJun 22, 2001
Also published asUS6685885
Publication number022670, 10022670, US 2003/0026735 A1, US 2003/026735 A1, US 20030026735 A1, US 20030026735A1, US 2003026735 A1, US 2003026735A1, US-A1-20030026735, US-A1-2003026735, US2003/0026735A1, US2003/026735A1, US20030026735 A1, US20030026735A1, US2003026735 A1, US2003026735A1
InventorsDavid Nolte, Fred Regnier, Manoj Varma
Original AssigneeNolte David D., Regnier Fred E., Manoj Varma
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Bio-optical compact disk system
US 20030026735 A1
Abstract
A device for identifying analytes in a biological sample, including a substrate having a surface lying substantially in a first plane, a plurality of targets, each having a wall lying substantially in a second plane offset from the first plane, and a receptor coating applied to one of the surface and the target walls for binding analytes present in the biological sample when the biological sample is applied to the substrate. A laser beam is sequentially directed onto each of the plurality of target, the laser being positioned relative to the substrate such that when the beam is directed onto a target, a first half of the beam is reflected back to the laser from the wall of the target and a second half of the beam is reflected back to the laser from the surface of the substrate adjacent the target. The laser combines the first and second reflected halves to produce a diffraction signal that has a first value when an analyte is not bound to the receptor coating associated with a target and a second value when an analyte is bound to the receptor coating associated with the target, thereby indicating the presence of the analyte.
Images(10)
Previous page
Next page
Claims(23)
What is claimed is:
1. A device for identifying analytes in a biological sample, including: a substrate having a plurality of pits, each of the pits extending into the substrate from a land area to a bottom wall having a receptor coating thereon for binding analytes upon application of the biological sample to the substrate;
a laser including a beam that is sequentially directed into each of the plurality of pits;
wherein when an analyte is not bound to a receptor coating of a pit, a portion of the beam reflected off the coating is combined with a portion of the beam reflected off the land area to produce a first diffraction signal, and when an analyte is bound to the coating, a portion of the beam reflected off the bound analyte is combined with a portion of the beam reflected off the land area to produce a second diffraction signal, thereby indicating the presence of the analyte.
2. The device of claim 1 wherein the land areas of the plurality of pits lie in a first plane, and the bottom walls of the pits lie in a second plane at a distance from the first plane.
3. The device of claim 2 wherein the distance is approximately one-eighth the distance of a wavelength of the beam.
4. The device of claim 2 wherein the distance is approximately one-fourth the distance of a wavelength of the beam.
5. The device of claim 1 wherein the device functions as a homodyne optical detector operating in quadrature.
6. The device of claim 1 wherein the substrate is a compact disk.
7. The device of claim 1 further including a motor for rotating the substrate.
8. The device of claim 1 wherein the portion of the beam reflected off the coating is approximately fifty percent of the total area of the beam that is reflected off the substrate.
9. The device of claim 1 wherein the portion of the beam reflected off the coating has a first intensity and the portion of the beam reflected off the land area has a second intensity, the first intensity being phase shifted relative to the second intensity.
10. The device of claim 9 wherein the phase shift is approximately π/2.
11. The device of claim 9 wherein the phase shift is greater than zero and less than π.
12. A device for identifying analytes in a biological sample, including:
a substrate having a surface lying substantially in a first plane, a plurality of targets offset vertically from the substrate surface, each of the targets having wall lying substantially in a second plane, and a receptor coating applied to one of the surface and the walls of the targets for binding analytes present in the biological sample when the biological sample is applied to the substrate;
a laser for sequentially directing a beam at each of the plurality of targets, the laser being positioned relative to the substrate such that when the beam is directed at a target, a first half of the beam is reflected back to the laser from the target wall and a second half of the beam is reflected back to the laser from the surface of the substrate adjacent the target, the laser combining the first and second reflected halves to produce a diffraction signal;
wherein the diffraction signal has a first value when an analyte is not bound to the receptor coating associated with a target and a second value when an analyte is bound to the receptor coating associated with the target, thereby indicating the presence of the analyte.
13. The device of claim 12 wherein each target functions as an independent interferometer.
14. A device for identifying analytes in a biological sample, including:
a substrate having a plurality of mesas formed thereon, each of the mesas extending above the substrate from a land area and having an upper surface with a receptor coating thereon for binding analytes upon application of the biological sample to the substrate;
a laser including a beam that is sequentially directed onto each of the plurality of mesas;
wherein when an analyte is not bound to a receptor coating of a mesa, a portion of the beam reflected off the coating is combined with a portion of the beam reflected off the land area to produce a first diffraction signal, and when an analyte is bound to the coating, a portion of the beam reflected off the bound analyte is combined with a portion of the beam reflected off the land area to produce a second diffraction signal, thereby indicating the presence of the analyte.
15. The device of claim 14 wherein the land areas of the plurality of mesas lie in a first plane, and the upper surfaces of the mesas lie in a second plane at a distance from the first plane.
16. The device of claim 15 wherein the distance is approximately one-eighth the distance of a wavelength of the beam.
17. The device of claim 15 wherein the distance is approximately one-fourth the distance of a wavelength of the beam.
18. The device of claim 14 wherein the device functions as a homodyne optical detector operating in quadrature.
19. The device of claim 14 wherein the substrate is a compact disk.
20. The device of claim 14 wherein the portion of the beam reflected off the coating is approximately fifty percent of the total area of the beam that is reflected off the substrate.
21. The device of claim 14 wherein the portion of the beam reflected off the coating has a first intensity and the portion of the beam reflected off the land area has a second intensity, the first intensity being phase shifted relative to the second intensity.
22. The device of claim 21 wherein the phase shift is approximately π/2.
23. The device of claim 21 wherein the phase shift is greater than zero and less than π.
Description
  • [0001]
    This application claims the benefit of U.S. Provisional Application Serial No. 60/300,277, filed on Jun. 22, 2001, which is incorporated herein by reference.
  • FIELD OF THE INVENTION
  • [0002]
    The present invention generally relates to a device for detecting the presence of specific biological material in a sample, and more particularly to a laser compact disc system for detecting the presence of biological pathogens and/or analyte molecules bound to target receptors on the disc by sensing changes in the far-field diffracted intensity of the light along the optic axis of the laser caused by the pathogens and/or analytes.
  • BACKGROUND OF THE INVENTION
  • [0003]
    In many chemical, biological, medical, and diagnostic applications, it is desirable to detect the presence of specific molecular structures in a sample. Many molecular structures such as cells, viruses, bacteria, toxins, peptides, DNA fragments, and antibodies are recognized by particular receptors. Biochemical technologies including gene chips, immulogical chips, and DNA arrays for detecting gene expression patterns in cancer cells, exploit the interaction between these molecular structures and the receptors as described in document numbers 8-11 of the list of documents provided at the end of this specification, all of which are hereby expressly incorporated herein by reference. These technologies generally employ a stationary chip prepared to include the desired receptors (those which interact with the molecular structure under test or analyte). Since the receptor areas can be quite small, chips may be produced which test for a plurality of analytes. Ideally, many thousand binding receptors are provided to provide a complete assay. When the receptors are exposed to a biological sample, only a few may bind a specific protein or pathogen. Ideally, these receptor sites are identified in as short a time as possible.
  • [0004]
    One such technology for screening for a plurality of molecular structures is the so-called immunlogical compact disk, which simply includes an antibody microarray. [See documents 16-18]. Conventional fluorescence detection is employed to sense the presence in the microarray of the molecular structures under test. This approach, however, is characterized by the known deficiencies of fluorescence detection, and fails to provide a capability for performing rapid repetitive scanning.
  • [0005]
    Other approaches to immunological assays employ traditional Mach-Zender interferometers that include waveguides and grating couplers. [See documents 19-23]. However, these approaches require high levels of surface integration, and do not provide high-density, and hence high-throughput, multi-analyte capabilities.
  • SUMMARY OF THE INVENTION
  • [0006]
    The present invention provides a biological, optical compact disk (“bio-optical CD”) system including a CD player for scanning biological CDs, which permit use of an interferometric detection technique to sense the presence of particular analyte in a biological sample. In one embodiment, binding receptors are deposited in the metallized pits of the CD (or grooves, depending upon the structure of the CD) using direct mechanical stamping or soft lithography. [See document 1-7]. In another embodiment, mesas or ridges are used instead of pits. Since inkpad stamps can be small (on the order of a square millimeter), the chemistry of successive areas of only a square millimeter of the CD may be modified to bind different analyte. A CD may include ten thousand different “squares” of different chemistry, each including 100,000 pits prepared to bind different analyte. Accordingly, a single CD could be used to screen for 10,000 proteins in blood to provide an unambiguous flood screening.
  • [0007]
    Once a CD is prepared and exposed to a biological sample, it is scanned by the laser head of a modified CD player which detects the optical signatures (such as changes in refraction, surface shape, or absorption) of the biological structures bound to the receptors within the pits. In general, each pit is used as a wavefront-splitting interferometer wherein the presence of a biological structure in the pit affects the characteristics of the light reflected from the pit, thereby exploiting the high sensitivity associated with interferometeric detection. For large analytes such as cells, viruses and bacteria, the interferemeter of each pit is operated in a balanced condition wherein the pit depth is λ4. For small analytes such as low-molecular weight antigens where very high sensitivity is desirable, each pit interferometer is operated in a phase-quadrature condition wherein the pit depth is λ/8. The sensitivity can be increased significantly by incorporating a homodyne detection scheme, using a sampling rate of 1 Mbps with a resolution bandwidth of less than 1 kHz. Since pit-to-pit scan times are less than a microsecond, one million target receptors may be assessed in one second.
  • [0008]
    These and other features of the invention will become more apparent and the invention will be better understood upon review of the following specifications and accompanying drawings.
  • BRIEF DESCRIPTION OF THE DRAWINGS
  • [0009]
    [0009]FIG. 1 is a block diagram of a bio-optical CD system according to the present invention.
  • [0010]
    [0010]FIG. 2 is a top plan view of a portion of a CD.
  • [0011]
    [0011]FIGS. 3A and 3B are cross-sectional views taken substantially along lines 3A-3A and 3B-3B of FIG. 2, respectively.
  • [0012]
    [0012]FIG. 4 is a plot of the far-field diffraction of a balanced system and a system that is 20% off the balanced condition.
  • [0013]
    [0013]FIG. 5 is a plot of the far-field diffraction of a balanced system and a system operating in a condition of quadrature.
  • [0014]
    [0014]FIG. 6 is a plot of the universal response curve of interferometers.
  • [0015]
    [0015]FIG. 7 is a block diagram of the optical train of a laser according to the present invention.
  • [0016]
    [0016]FIGS. 8 and 9 are conceptual diagrams of processes for applying receptor coatings to portions of a CD.
  • [0017]
    [0017]FIG. 10 is a conceptual diagram of a method for delivering a biological sample to areas of a CD.
  • DESCRIPTION OF EMBODIMENTS OF THE INVENTION
  • [0018]
    The embodiments described below are merely exemplary and are not intended to limit the invention to the precise forms disclosed. Instead, the embodiments were selected for description to enable one of ordinary skill in the art to practice the invention.
  • [0019]
    Referring now to FIG. 1, a bio-optical CD system according to the present invention generally includes a CD player 10 for scanning a removable biological CD 12. CD player 10 may be a conventional, commercial CD player modified as described herein. CD player 10 includes a motor 14, a laser 16, control electronics 18, and output electronics 20. As should be apparent to one of ordinary skill in the art, the block diagram of FIG. 1 is greatly simplified, and intended merely to suggest basic components of the well-known construction of a conventional CD player. In general, control electronics 18 control the operation of laser 16 and motor 14. Motor 14 rotates CD 12. Laser 16 obtains optical information from CD 12 as is further described below. This information is then communicated to external electronics (not shown) through output electronics 20.
  • [0020]
    As shown in FIG. 2, CD 12 includes a substrate having a plurality of pits 22A-C (three shown) arranged on a plurality of tracks 24 (one shown).). It should be understood that, while the present disclosure refers to the targets of laser 16 as “pits,” one of ordinary skill in the art could readily utilize the teachings of the invention on a CD formed with targets having different shapes, such as grooves. Moreover, as is further described below, the targets could be small plateaus, or mesas formed on the surface of the CD.
  • [0021]
    Pits 22A-C and tracks 24 are separated by flat areas of the surface of CD 12 referred to as the land 25. Each pit 22 respectively includes a sidewall 27 that extends at an angle, for example, substantially perpendicularly into the body of CD 12, and a bottom wall 29 which lies in a plane below, and substantially parallel with the plane containing land 25. According to well-established principles in the art, as CD 12 rotates, pits 22 of each track 25 move under a laser beam 26 from laser 16. After each track 25 of pits 22 is scanned, laser 16 moves laser beam 26 radially relative to the center of CD 12 to the next track 25. In this manner, laser beam 26 sequentially scans each track 25 of CD 12 until the entire area of CD 12 is scanned. It should be understood, however, that if CD 12 is formed to contain a single, spiral shaped track 25, instead of the concentric circular tracks 25 described above, laser beam 26 moves in a substantially continuous radial manner to follow the spiral of the spiral shaped track 25.
  • [0022]
    The size and position of beam 26 relative to pit 22B, for example, results in 50% of the beam area (area A1 plus area A2) reflecting off land 25, and 50% of the beam area (A3) reflecting off bottom wall 29B. Thus, CD 12 is scanned using principles of a 50/50 wavefront-splitting interferometer, as further described below.
  • [0023]
    [0023]FIG. 3A is a cross-sectional view of pit 22A under laser beam 26. A representative light ray R1 is shown reflecting off land 25 within area A1, and a ray R2 is shown reflecting off bottom wall 29A having a thin applied antibody or receptor coating 30A. Pit 22A is shown having a depth of λ/x. Pits of conventional CDs have a depth of λ/4. On double pass (on reflection), this depth imparts a π phase shift to the light incident in pit 22A relative to the light incident on areas A1 and A2 of land 25. In other words, because the distance traveled by ray R2 is approximately λ/2 times greater than the distance traveled by ray R1 (λ/4 down pit 22A plus λ/4 up pit 22A, ignoring the thickness of coating 30A), the reflected ray R2 appears phase shifted by one-half of one wavelength. As explained with reference to FIG. 2, the intensity of light incident on pit 22A (within area A3) is balanced by the intensity of light on land 25 (within areas A1 and A2). The equal reflected amplitudes and the π phase difference between the light reflected from pit 22A and land 25 cause cancellation of the far-field diffracted intensity along the optic axis. The presence of pit 22A is therefore detected as an intensity drop-out as laser 16 scans over the surface of CD 12. This drop out is due to the destructive interference of the light from land 25 and pit 22A. Splitting the amplitude between pit 22A and land 25 creates the 50/50 wavefront splitting interferometer. [See document 24].
  • [0024]
    The far-field diffraction of pit 22A is shown as signal 32 in FIG. 4 for the balanced condition with a π phase difference between pit 22A and land 25. The intensity is cancelled by destructive interference along the optic axis. At finite angles, the intensity appears as diffraction orders. During immunological assays, it is common to use antibodies to bind large pathogens such as cells and bacteria. These analytes are large, comprising a large fraction of the wavelength of light. For instance, the bacterium E coli has a width of approximately 0.1 microns and a length of about 1 micron. While this bacterium is small enough to fit into a pit 22A-C, it is large enough to produce a large phase change from the pit 22A-C upon binding.
  • [0025]
    In this situation of a large analyte, the interferometer is best operated in the balanced condition described above. The presence of the analyte is detected directly as a removal of the perfect destructive interference that occurs in the absence of the bound pathogen as described below. It should also be understood that to improve detection sensitivity, it is possible to attach tags to bound analytes that can turn small analytes into effective large analytes. Conversely, sandwich structures can be used to bind additional antibodies to the bound analytes that can improve the responsivity of the detection.
  • [0026]
    When the balanced phase condition is removed, only partial destructive interference occurs. Referring to FIG. 3B, pit 22B is shown under beam 26. The structure of pit 22B of FIG. 3B is identical to that of pit 22A of FIG. 3A, except that receptor coating 30B has attracted a molecular structure 34 from the biological sample under test. Molecular structure 34 is shown as having a thickness T. As light ray R2 travels through thickness T of structure 34, ray 32 acquires additional phase because of the refractive index of structure 34. Specifically, since pit 22B has a depth of λ/4 (like pit 22A of FIG. 3A), and structure 34 has a thickness T, ray R2 travels in a manner that yields a phase shift of some percentage of λ/2. Assuming T is sufficiently large to result in a phase difference of 0.8*(λ/2), a diffraction signal 36 results as shown in FIG. 4. Signal 36 is approximately 10% (relative to 100% for light incident entirely on land 25) greater at a far-field diffraction angle of zero. Accordingly, one embodiment of a system of the present invention may detect the presence of particular molecular structures within a biological sample by detecting changes in diffraction signal as described above.
  • [0027]
    It should be apparent that since the system detects changes in intensity of light from one area (A3) relative to light reflected from another area (A1 plus A2), land 25 could be coated with receptor coating (not shown) instead of bottom walls 29A-C of pits 22A-C to yield the same result. In such an embodiment, molecular structure 34 binds to the coating (not shown) on land 25 adjacent pit 22A-C, thereby affecting the phase of representative light ray R1. This difference manifests itself as a change in the diffraction signal in the manner described above.
  • [0028]
    As indicated above, in an alternate embodiment of the invention, mesas are used instead of pits 22A-C. According to this embodiment, flat plateaus or mesas are formed at spaced intervals along tracks 25. Such mesas may be formed using conventional etching techniques, or more preferably, using deposition techniques associated with metalization. All of the above teachings apply in principle to a CD 12 have mesas instead of pits 22A-C. More specifically, it is conceptually irrelevant whether rays R1 and R2 acquire phase changes due to the increased travel of ray R2 into a depression or pit, or due to the reduced travel of ray R2 as it is reflected off the upper wall of a raised plateau or mesa. It is the difference between the travel path of ray R2 and that of ray R1 that creates the desired result.
  • [0029]
    Alternatively, because some cells and bacteria are comparable in size to the wavelength of light, it should also be possible to detect them directly on a flat surface uniformly coated with antibodies rather than bound in or around pits 22A-C. This has the distinct advantage that no pit (or mesa) fabrication is needed, and the targets can be patterned into strips that form diffraction gratings (see Ref. 27&28). Alternatively, it is often adequate in an immunological assay simply to measure the area density of bacteria. As laser 16 scans over the bacterium, the phase of the reflected light changes relative to land 25 surrounding the bacterium. This causes partial destructive interference that is detected as dips in the reflected intensity.
  • [0030]
    The contrast between the balanced (empty) pit and the binding pit can be large. However, high signal-to-noise-ratio (SNR) requires high intensities, which is not the case when the interferometer is balanced. Accordingly, another embodiment of the present invention employs homodyne detection that uses pit depths resulting in amplitudes from the pit and land in a condition of phase-quadrature as described below.
  • [0031]
    Phase-quadrature is attained when the two amplitudes (the light intensity reflected from pit 22A, for example, and the light intensity reflected from areas A1 and A2 of land 25 surrounding pit 22A) differ by a phase of π/2. This condition thus requires a pit depth of λ/8. It is well-known that the quadrature condition yields maximum linear signal detection in an interferometer. [See document 25]. The far-field diffraction of a pit in the condition of quadrature is shown as signal 38 in FIG. 5. In this condition, very small changes in the relative phase of the pit and land cause relatively large changes in the intensity along the optic axis. For example, a phase change of only 0.05*(λ/2) produces the same magnitude change in the diffracted signal as the relatively large phase change of 0.2*(λ/2) which resulted in signal 36 of FIG. 4. Accordingly, the condition of quadrature provides much higher sensitivity for detection of small bound molecular structures.
  • [0032]
    [0032]FIG. 6 further depicts the differences in response characteristics of the two modes of operation described above. Curve 40 represents the universal response curve of all interferometers. Optical CD systems operating in a balanced condition as described above function at and around the point 42 of curve 40 corresponding to λ/2 on the x-axis of the figure. As should be apparent from the drawing, changes in the measured response (for example, light reflection) resulting from changes due to the presence of the sensed molecular structure (for example, the distance traveled by ray R2 of FIGS. 3A, 3B), are relatively small when operating about point 42 because of the low slope of curve 40. Specifically, a change of X1 along the x-axis of FIG. 6 results in a change in response of Y1.
  • [0033]
    When operating in the condition of quadrature, on the other hand, a CD system according to the present invention operates at and around the point 44 of curve 40 corresponding to λ/4 on the x-axis of FIG. 6. Clearly, this area of curve 40 yields a more responsive system because of its increased slope. As shown, the same change of X1 that resulted in a change in response of Y1 relative to point 42 yields a much greater change in response of Y2 relative to point 44.
  • [0034]
    As should be apparent from the foregoing, regardless of the depth of pits 22A-C, or even whether pits are used at all, the presence or absence of analytes creates a phase modulated signal, which conveys the screening information. If one desires to maintain a quadrature condition and its associated increased sensitivity, the technology described in U.S. Pat. No. 5,900,935, which is incorporated herein by reference, may be adapted. Instead of a phase modulated signal from an ultrasound source, the present invention so adapted provides a phase modulated signal from analytes as described above.
  • [0035]
    It is possible to derive equations describing the fundamental SNR for detection in quadrature as a homodyne detection process. The intensity along the optic axis of the detection system when it is in quadrature is given by I = ( I 1 + I 2 ) ( 1 + m cos ( π 4 + δ ) ) ( 1 )
  • [0036]
    where I1 and I2 are the intensities reflected from land 25 and a particular pit 22A-C. The phase shift of the light reflected from pit 22A-C is δ = 4 π λ Δ n d An ( 2 )
  • [0037]
    where Δn is the change in refractive index cause by the bound molecular structure, and dAn is the thickness of the bound molecular structure. The contrast index m is given by m = 2 I 1 I 2 I 1 + I 2 ( 3 )
  • [0038]
    For ideal operation, P1=P2, P=P1+P2, and m=1.
  • [0039]
    For small phase excursions, the signal detected from Eq. 1 becomes S = P 2 hv m 4 π λ Δ n d An ( 4 )
  • [0040]
    in terms of the total detected powers P and where hv is the photon energy. There are three sources of noise in this detection system: 1) shot noise of the light from beam 26; 2) binding statistics of the antibodies; and 3) bonding statistics of the bound analyte. The shot noise is given by N shot = P hv BW ( 5 )
  • [0041]
    where BW is the detection bandwidth of the detection system. The noise from the fluctuations in the bound antibody is given by (assuming random statistics) N Ab = P hv m 4 π λ Δ n Ab M Ab d Ab 0 ( 6 )
  • [0042]
    and for the bound analyte is N An = P hv BW m 4 π λ Δ n An M An d An 0 ( 7 )
  • [0043]
    where MAb and MAn are the number of bound antibody and analyte molecules, and d0 An and d0 Ab are the effective thicknesses of a single bound molecule given by
  • Ad0 An =V 0 An  (8)
  • [0044]
    where A is the area of pit 22A-C and V0 An is the molecular volume.
  • [0045]
    The smallest number of analyte molecules that can be detected for a SNR equal to unity, assuming the analyte fluctuation noise equals the shot noise, is given by the NEM (noise-equivalent molecules) NEM = hv BW P ( λ 4 πΔ n An d An 0 ) 2 ( 9 )
  • [0046]
    A detected power of 1 milliwatt and a detection bandwidth of 1 Hz, assuming Δn=0.1 and d0 An=0.01 picometer, yields a one-molecule sensitivity of
  • NEM≈1
  • [0047]
    This achieves sensitivity for single molecule detection with a SNR of unity. To achieve a SNR of 100:1 would require 10,000 bound molecular structures.
  • [0048]
    An alternative (and useful) way of looking at noise is to calculate the noise-equivalent power (NEP) of the system. This is defined as the power needed for the shot noise contribution to equal the other noise contributions to the total noise. Assuming that the antibody layer thickness fluctuations dominate the noise of the system, the NEP is obtained by equating Eq. 5 with Eq. 6. The resulting NEP is NEP = hv BW ( 4 π Δ n Ab ) 2 M Ab ( λ d Ab 0 ) 2 ( 10 )
  • [0049]
    If an antibody layer thickness of 0.01 pm and a refractive index change of 0.1 are assumed, the resulting NEP is 1 milliwatts•molecules. If there are 105 bound antibodies in a pit (or within the radius of the probe laser), then the power at which the shot noise equals the noise from the fluctuating antibody layer thickness is only
  • NEP=10 nWatts/Hz
  • [0050]
    Accordingly, probe spot powers greater than 10 nW will cause the noise to be dominated by the fluctuating antibody layer thickness rather than by the shot noise. The NEP is therefore an estimate of the required power of laser 16. In this case, the power is extremely small, avoiding severe heating.
  • [0051]
    [0051]FIG. 7 depicts an optical train 50 included within laser 16 of FIG. 1 for detecting bound analytes. Optical train 50 is identical to to conventional optical trains currently used in commercial CD-ROM disks. Vertical tracking is accomplished “on-the-fly” using a four-quadrant detector 52 and a servo-controlled voice coil to maintain focus on the plane of spinning CD 12. Likewise, lateral tracking uses two satellite laser spots 54 (FIG. 2) with a servo-controlled voice coil to keep probe laser spot 26 on track 24. This approach uses the well-developed tracking systems that have already been efficiently engineered for conventional CD players. The high-speed real-time tracking capabilities of the servo-control systems allows CD 12 to spin at a rotation of 223 rpm and a linear velocity at the rim of 1.4 m/sec. The sampling rate is 4 Msamp/sec, representing very high throughput for an immunological assay. The ability to encode identification information directly onto CD 12 using conventional CD coding also makes the use of the CD technology particularly attractive, as patented in U.S. Pat. No. 6,110,748.
  • Priming the CD 12
  • [0052]
    CD 12 can be charged using novel inkpad stamp technology [see documents 1-7] shown in FIGS. 8 and 9. Either land 25 or pits 22A-C can be primed with antibody layer 30. To prime land 25, the antibodies coated on the inkpad 58 attach only on land 25 that is in contact with pads 22A-C, as shown in FIG. 8. Analytes bound on land 25 are equally capable of changing the far-field diffraction as analytes bound to the pits 22A-C. Of course, as described below, the antibodies may be coated (receptor coating 30) on bottom wall 29A-C of pits 22A-C.
  • [0053]
    Referring now to FIG. 9, to prime antibodies in pits 22A-C, first a blocking layer 60 can be applied to land 25 that prevents the adhesion of antibodies 30. Later, the area is flooded with antibodies 30 that only attach in exposed pits 22A-C. Blocking layer 60 can later be removed to improve the sensitivity of the optical detection (by removing the contribution to the total noise of the detection system of the fluctuations of the thickness of blocking layer 60).
  • Delivery of the Biological Samples
  • [0054]
    The delivery of biological samples containing analytes to the primed areas of bio-CD 12 (i.e., pits 22A-C, land 25, or simply a flat surface of CD 12) can be accomplished using microfluidic channels 56 fabricated in CD 12, as shown in FIG. 10. Microfluidic channels 56 can plumb to all pits 22A-C. Alternatively, the biological sample can flow over land 25. The advantages in spinning CD 12 is the use of centrifugal force F to pull the fluid biological sample from the delivery area near the central axis A over the entire surface of CD 12 as an apparent centrifuge, as in U.S. Pat. No. 6,063,589. Similarly, capillary forces can be used to move the fluid through microchannels 56. This technique of biological sample distribution can use micro-fluidic channels 56 that are lithographically defined at the same time CD pits 22A-C are defined.
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US6980299Oct 16, 2002Dec 27, 2005General Hospital CorporationSystems and methods for imaging a sample
US7659968Feb 9, 2010Purdue Research FoundationSystem with extended range of molecular sensing through integrated multi-modal data acquisition
US7663092Feb 1, 2006Feb 16, 2010Purdue Research FoundationMethod and apparatus for phase contrast quadrature interferometric detection of an immunoassay
US7724786Apr 11, 2008May 25, 2010The General Hospital CorporationProcess and apparatus for a wavelength tuning source
US7733497Sep 8, 2004Jun 8, 2010The General Hospital CorporationMethod and apparatus for performing optical imaging using frequency-domain interferometry
US7742173Jun 22, 2010The General Hospital CorporationMethods, arrangements and systems for polarization-sensitive optical frequency domain imaging of a sample
US7761139Jan 26, 2004Jul 20, 2010The General Hospital CorporationSystem and method for identifying tissue using low-coherence interferometry
US7782464May 4, 2007Aug 24, 2010The General Hospital CorporationProcesses, arrangements and systems for providing a fiber layer thickness map based on optical coherence tomography images
US7787126Aug 31, 2010Purdue Research FoundationMethod and apparatus for conjugate quadrature interferometric detection of an immunoassay
US7796270Jan 10, 2007Sep 14, 2010The General Hospital CorporationSystems and methods for generating data based on one or more spectrally-encoded endoscopy techniques
US7797119Sep 14, 2010The General Hospital CorporationApparatus and method for rangings and noise reduction of low coherence interferometry LCI and optical coherence tomography OCT signals by parallel detection of spectral bands
US7809225Sep 5, 2008Oct 5, 2010The General Hospital CorporationImaging system and related techniques
US7809226Sep 5, 2008Oct 5, 2010The General Hospital CorporationImaging system and related techniques
US7843572Sep 29, 2006Nov 30, 2010The General Hospital CorporationMethod and apparatus for optical imaging via spectral encoding
US7847949Dec 7, 2010The General Hospital CorporationMethod and apparatus for optical imaging via spectral encoding
US7859679May 31, 2006Dec 28, 2010The General Hospital CorporationSystem, method and arrangement which can use spectral encoding heterodyne interferometry techniques for imaging
US7865231May 1, 2002Jan 4, 2011The General Hospital CorporationMethod and apparatus for determination of atherosclerotic plaque type by measurement of tissue optical properties
US7872757Sep 30, 2009Jan 18, 2011The General Hospital CorporationApparatus and method for ranging and noise reduction of low coherence interferometry LCI and optical coherence tomography OCT signals by parallel detection of spectral bands
US7872759Sep 29, 2006Jan 18, 2011The General Hospital CorporationArrangements and methods for providing multimodality microscopic imaging of one or more biological structures
US7889348Feb 15, 2011The General Hospital CorporationArrangements and methods for facilitating photoluminescence imaging
US7903257Mar 8, 2011The General Hospital CorporationApparatus and method for ranging and noise reduction of low coherence interferometry (LCI) and optical coherence tomography (OCT) signals by parallel detection of spectral bands
US7910356Feb 1, 2006Mar 22, 2011Purdue Research FoundationMultiplexed biological analyzer planar array apparatus and methods
US7911621Mar 22, 2011The General Hospital CorporationApparatus and method for controlling ranging depth in optical frequency domain imaging
US7920271Apr 5, 2011The General Hospital CorporationApparatus and methods for enhancing optical coherence tomography imaging using volumetric filtering techniques
US7925133Apr 12, 2011The General Hospital CorporationImaging system and related techniques
US7933021Oct 30, 2008Apr 26, 2011The General Hospital CorporationSystem and method for cladding mode detection
US7949019May 24, 2011The General HospitalWavelength tuning source based on a rotatable reflector
US7969578Jun 13, 2008Jun 28, 2011The General Hospital CorporationMethod and apparatus for performing optical imaging using frequency-domain interferometry
US7982879Jul 19, 2011The General Hospital CorporationMethods and systems for performing angle-resolved fourier-domain optical coherence tomography
US7995210Nov 21, 2005Aug 9, 2011The General Hospital CorporationDevices and arrangements for performing coherence range imaging using a common path interferometer
US7995627Nov 30, 2009Aug 9, 2011The General Hospital CorporationProcess and apparatus for a wavelength tuning source
US8018598Jul 23, 2004Sep 13, 2011The General Hospital CorporationProcess, system and software arrangement for a chromatic dispersion compensation using reflective layers in optical coherence tomography (OCT) imaging
US8032200Sep 21, 2006Oct 4, 2011The General Hospital CorporationMethods and systems for tissue analysis
US8040608Oct 18, 2011The General Hospital CorporationSystem and method for self-interference fluorescence microscopy, and computer-accessible medium associated therewith
US8045177Oct 25, 2011The General Hospital CorporationApparatus and methods for measuring vibrations using spectrally-encoded endoscopy
US8050747Nov 1, 2011The General Hospital CorporationMethod and apparatus for determination of atherosclerotic plaque type by measurement of tissue optical properties
US8054468Dec 13, 2007Nov 8, 2011The General Hospital CorporationApparatus and method for ranging and noise reduction of low coherence interferometry LCI and optical coherence tomography OCT signals by parallel detection of spectral bands
US8072585Dec 6, 2011Purdue Research FoundationSystem with extended range of molecular sensing through integrated multi-modal data acquisition
US8081316Aug 8, 2005Dec 20, 2011The General Hospital CorporationProcess, system and software arrangement for determining at least one location in a sample using an optical coherence tomography
US8097864Jan 17, 2012The General Hospital CorporationSystem, method and computer-accessible medium for providing wide-field superresolution microscopy
US8115919May 2, 2008Feb 14, 2012The General Hospital CorporationMethods, arrangements and systems for obtaining information associated with a sample using optical microscopy
US8145018Mar 27, 2012The General Hospital CorporationApparatus for obtaining information for a structure using spectrally-encoded endoscopy techniques and methods for producing one or more optical arrangements
US8149418Oct 22, 2010Apr 3, 2012The General Hospital CorporationMethod and apparatus for optical imaging via spectral encoding
US8150496Aug 8, 2008Apr 3, 2012The General Hospital CorporationMethod and apparatus for determination of atherosclerotic plaque type by measurement of tissue optical properties
US8174702Jul 27, 2009May 8, 2012The General Hospital CorporationSpeckle reduction in optical coherence tomography by path length encoded angular compounding
US8175685May 4, 2007May 8, 2012The General Hospital CorporationProcess, arrangements and systems for providing frequency domain imaging of a sample
US8208995Aug 24, 2005Jun 26, 2012The General Hospital CorporationMethod and apparatus for imaging of vessel segments
US8289522Oct 16, 2012The General Hospital CorporationArrangements and methods for providing multimodality microscopic imaging of one or more biological structures
US8298831May 15, 2009Oct 30, 2012Purdue Research FoundationDifferentially encoded biological analyzer planar array apparatus and methods
US8305585May 28, 2010Nov 6, 2012Pall CorporationFiber-optic assay apparatus based on phase-shift interferometry
US8351665Apr 28, 2006Jan 8, 2013The General Hospital CorporationSystems, processes and software arrangements for evaluating information associated with an anatomical structure by an optical coherence ranging technique
US8355138Jan 15, 2013The General Hospital CorporationMethod and apparatus for performing optical imaging using frequency-domain interferometry
US8369669Apr 11, 2011Feb 5, 2013The General Hospital CorporationImaging system and related techniques
US8384907Feb 26, 2013The General Hospital CorporationMethod and apparatus for optical imaging via spectral encoding
US8384909Jun 7, 2010Feb 26, 2013The General Hospital CorporationMethod and apparatus for performing optical imaging using frequency-domain interferometry
US8416818Apr 9, 2013The General Hospital CorporationProcess and apparatus for a wavelength tuning source
US8559012May 7, 2012Oct 15, 2013The General Hospital CorporationSpeckle reduction in optical coherence tomography by path length encoded angular compounding
US8593619May 7, 2009Nov 26, 2013The General Hospital CorporationSystem, method and computer-accessible medium for tracking vessel motion during three-dimensional coronary artery microscopy
US8647588May 4, 2011Feb 11, 2014Pall CorporationTip tray assembly for optical sensors
US8676013Feb 4, 2013Mar 18, 2014The General Hospital CorporationImaging system using and related techniques
US8705046Dec 19, 2012Apr 22, 2014The General Hospital CorporationMethod and apparatus for performing optical imaging using frequency-domain interferometry
US8721077Apr 26, 2012May 13, 2014The General Hospital CorporationSystems, methods and computer-readable medium for determining depth-resolved physical and/or optical properties of scattering media by analyzing measured data over a range of depths
US8760663Apr 2, 2012Jun 24, 2014The General Hospital CorporationMethod and apparatus for optical imaging via spectral encoding
US8804126Mar 7, 2011Aug 12, 2014The General Hospital CorporationSystems, methods and computer-accessible medium which provide microscopic images of at least one anatomical structure at a particular resolution
US8818149Mar 22, 2012Aug 26, 2014The General Hospital CorporationSpectrally-encoded endoscopy techniques, apparatus and methods
US8838213Oct 19, 2007Sep 16, 2014The General Hospital CorporationApparatus and method for obtaining and providing imaging information associated with at least one portion of a sample, and effecting such portion(s)
US8861910Jun 19, 2009Oct 14, 2014The General Hospital CorporationFused fiber optic coupler arrangement and method for use thereof
US8896838Mar 7, 2011Nov 25, 2014The General Hospital CorporationSystems, methods and computer-accessible medium which provide microscopic images of at least one anatomical structure at a particular resolution
US8922781Nov 29, 2005Dec 30, 2014The General Hospital CorporationArrangements, devices, endoscopes, catheters and methods for performing optical imaging by simultaneously illuminating and detecting multiple points on a sample
US8928889Oct 8, 2012Jan 6, 2015The General Hospital CorporationArrangements and methods for providing multimodality microscopic imaging of one or more biological structures
US8937724Dec 10, 2009Jan 20, 2015The General Hospital CorporationSystems and methods for extending imaging depth range of optical coherence tomography through optical sub-sampling
US8965487Aug 24, 2005Feb 24, 2015The General Hospital CorporationProcess, system and software arrangement for measuring a mechanical strain and elastic properties of a sample
US9060689Jun 1, 2006Jun 23, 2015The General Hospital CorporationApparatus, method and system for performing phase-resolved optical frequency domain imaging
US9069130May 3, 2010Jun 30, 2015The General Hospital CorporationApparatus, method and system for generating optical radiation from biological gain media
US9081148Mar 7, 2011Jul 14, 2015The General Hospital CorporationSystems, methods and computer-accessible medium which provide microscopic images of at least one anatomical structure at a particular resolution
US9087368Jan 19, 2007Jul 21, 2015The General Hospital CorporationMethods and systems for optical imaging or epithelial luminal organs by beam scanning thereof
US9173572Nov 25, 2013Nov 3, 2015The General Hospital CorporationSystem, method and computer-accessible medium for tracking vessel motion during three-dimensional coronary artery microscopy
US9176319Mar 21, 2008Nov 3, 2015The General Hospital CorporationMethods, arrangements and apparatus for utilizing a wavelength-swept laser using angular scanning and dispersion procedures
US9178330Feb 4, 2010Nov 3, 2015The General Hospital CorporationApparatus and method for utilization of a high-speed optical wavelength tuning source
US9186066Feb 1, 2007Nov 17, 2015The General Hospital CorporationApparatus for applying a plurality of electro-magnetic radiations to a sample
US9186067May 24, 2013Nov 17, 2015The General Hospital CorporationApparatus for applying a plurality of electro-magnetic radiations to a sample
US9226660Nov 16, 2011Jan 5, 2016The General Hospital CorporationProcess, system and software arrangement for determining at least one location in a sample using an optical coherence tomography
US9226665May 23, 2013Jan 5, 2016The General Hospital CorporationSpeckle reduction in optical coherence tomography by path length encoded angular compounding
US9254089Jul 14, 2009Feb 9, 2016The General Hospital CorporationApparatus and methods for facilitating at least partial overlap of dispersed ration on at least one sample
US9254102Sep 6, 2011Feb 9, 2016The General Hospital CorporationMethod and apparatus for imaging of vessel segments
US9282931Oct 3, 2011Mar 15, 2016The General Hospital CorporationMethods for tissue analysis
US9295391Nov 10, 2000Mar 29, 2016The General Hospital CorporationSpectrally encoded miniature endoscopic imaging probe
US9304121Feb 22, 2013Apr 5, 2016The General Hospital CorporationMethod and apparatus for optical imaging via spectral encoding
US20050018200 *Jan 10, 2003Jan 27, 2005Guillermo Tearney J.Apparatus for low coherence ranging
US20050018201 *Jan 24, 2003Jan 27, 2005De Boer Johannes FApparatus and method for ranging and noise reduction of low coherence interferometry lci and optical coherence tomography oct signals by parallel detection of spectral bands
US20050128488 *Nov 24, 2004Jun 16, 2005Dvir YelinMethod and apparatus for three-dimensional spectrally encoded imaging
US20050148063 *Dec 24, 2003Jul 7, 2005Cracauer Raymond F.Disposable reaction vessel with integrated optical elements
US20050280828 *Aug 25, 2005Dec 22, 2005The General Hospital CorporationSystems and methods for imaging a sample
US20060013544 *Jul 1, 2005Jan 19, 2006Bouma Brett EImaging system and related techniques
US20060055936 *Sep 12, 2005Mar 16, 2006The General Hospital CorporationSystem and method for optical coherence imaging
US20060058592 *Aug 24, 2005Mar 16, 2006The General Hospital CorporationProcess, system and software arrangement for measuring a mechanical strain and elastic properties of a sample
US20060058622 *Aug 24, 2005Mar 16, 2006The General Hospital CorporationMethod and apparatus for imaging of vessel segments
US20060067620 *Sep 29, 2005Mar 30, 2006The General Hospital CorporationSystem and method for optical coherence imaging
US20060093276 *Nov 2, 2005May 4, 2006The General Hospital CorporationFiber-optic rotational device, optical system and method for imaging a sample
US20060109478 *Nov 21, 2005May 25, 2006The General Hospital CorporationDevices and arrangements for performing coherence range imaging using a common path interferometer
US20060114473 *Nov 29, 2005Jun 1, 2006The General Hospital CorporationArrangements, devices, endoscopes, catheters and methods for performing optical imaging by simultaneously illuminating and detecting multiple points on a sample
US20060227333 *Mar 31, 2004Oct 12, 2006Tearney Guillermo JSpeckle reduction in optical coherence tomography by path length encoded angular compounding
US20060244973 *Sep 8, 2004Nov 2, 2006Seok-Hyun YunMethod and apparatus for performing optical imaging using frequency-domain interferometry
US20060270929 *May 31, 2006Nov 30, 2006The General Hospital CorporationSystem, method and arrangement which can use spectral encoding heterodyne interferometry techniques for imaging
US20060279742 *Jun 1, 2006Dec 14, 2006The General Hospital CorporationApparatus, method and system for performing phase-resolved optical frequency domain imaging
US20070003436 *Feb 1, 2006Jan 4, 2007Nolte David DMethod and apparatus for phase contrast quadrature interferometric detection of an immunoassay
US20070009935 *May 15, 2006Jan 11, 2007The General Hospital CorporationArrangements, systems and methods capable of providing spectral-domain optical coherence reflectometry for a sensitive detection of chemical and biological sample
US20070012886 *Apr 28, 2006Jan 18, 2007The General Hospital CorporationSystems. processes and software arrangements for evaluating information associated with an anatomical structure by an optical coherence ranging technique
US20070023643 *Feb 1, 2006Feb 1, 2007Nolte David DDifferentially encoded biological analyzer planar array apparatus and methods
US20070035743 *Aug 9, 2006Feb 15, 2007The General Hospital CorporationApparatus, methods and storage medium for performing polarization-based quadrature demodulation in optical coherence tomography
US20070038040 *Apr 24, 2006Feb 15, 2007The General Hospital CorporationArrangements, systems and methods capable of providing spectral-domain polarization-sensitive optical coherence tomography
US20070049833 *Aug 16, 2006Mar 1, 2007The General Hospital CorporationArrangements and methods for imaging in vessels
US20070073162 *Sep 21, 2006Mar 29, 2007The General Hospital CorporationMethods and systems for tissue analysis
US20070087445 *Oct 13, 2006Apr 19, 2007The General Hospital CorporationArrangements and methods for facilitating photoluminescence imaging
US20070121196 *Sep 29, 2006May 31, 2007The General Hospital CorporationMethod and apparatus for method for viewing and analyzing of one or more biological samples with progressively increasing resolutions
US20070171430 *Jan 18, 2007Jul 26, 2007The General Hospital CorporationSystems and methods for providing mirror tunnel micropscopy
US20070171433 *Jan 18, 2007Jul 26, 2007The General Hospital CorporationSystems and processes for providing endogenous molecular imaging with mid-infrared light
US20070177152 *Feb 1, 2007Aug 2, 2007The General Hospital CorporationMethods and systems for monitoring and obtaining information of at least one portion of a sample using conformal laser therapy procedures, and providing electromagnetic radiation thereto
US20070179487 *Feb 1, 2007Aug 2, 2007The General Hospital CorporationApparatus for applying a plurality of electro-magnetic radiations to a sample
US20070188855 *Jan 17, 2007Aug 16, 2007The General Hospital CorporationApparatus for obtaining information for a structure using spectrally-encoded endoscopy teachniques and methods for producing one or more optical arrangements
US20070201033 *Feb 21, 2007Aug 30, 2007The General Hospital CorporationMethods and systems for performing angle-resolved fourier-domain optical coherence tomography
US20070208400 *Mar 1, 2007Sep 6, 2007The General Hospital CorporationSystem and method for providing cell specific laser therapy of atherosclerotic plaques by targeting light absorbers in macrophages
US20070212257 *Feb 15, 2007Sep 13, 2007Purdue Research FoundationIn-line quadrature and anti-reflection enhanced phase quadrature interferometric detection
US20070223006 *Jan 18, 2007Sep 27, 2007The General Hospital CorporationSystems and methods for performing rapid fluorescence lifetime, excitation and emission spectral measurements
US20070229801 *Sep 29, 2006Oct 4, 2007The General Hospital CorporationArrangements and methods for providing multimodality microscopic imaging of one or more biological structures
US20070233396 *Sep 29, 2006Oct 4, 2007The General Hospital CorporationMethod and apparatus for optical imaging via spectral encoding
US20070259366 *May 3, 2007Nov 8, 2007Greg LawrenceDirect printing of patterned hydrophobic wells
US20070263227 *May 4, 2007Nov 15, 2007The General Hospital CorporationProcesses, arrangements and systems for providing a fiber layer thickness map based on optical coherence tomography images
US20070274650 *Feb 1, 2007Nov 29, 2007The General Hospital CorporationApparatus for controlling at least one of at least two sections of at least one fiber
US20070276269 *May 4, 2007Nov 29, 2007The General Hospital CorporationProcess, arrangements and systems for providing frequency domain imaging of a sample
US20070282403 *Feb 1, 2007Dec 6, 2007The General Hospital CorporationMethods and systems for providing electromagnetic radiation to at least one portion of a sample using conformal laser therapy procedures
US20080002211 *Jan 18, 2007Jan 3, 2008The General Hospital CorporationSystem, arrangement and process for providing speckle reductions using a wave front modulation for optical coherence tomography
US20080007734 *Oct 31, 2005Jan 10, 2008The General Hospital CorporationSystem and method for providing Jones matrix-based analysis to determine non-depolarizing polarization parameters using polarization-sensitive optical coherence tomography
US20080021275 *Jan 19, 2007Jan 24, 2008The General Hospital CorporationMethods and systems for optical imaging or epithelial luminal organs by beam scanning thereof
US20080049232 *Aug 24, 2007Feb 28, 2008The General Hospital CoporationApparatus and methods for enhancing optical coherence tomography imaging using volumetric filtering techniques
US20080094637 *Dec 13, 2007Apr 24, 2008The General Hospital CorporationApparatus and method for ranging and noise reduction of low coherence interferometry lci and optical coherence tomography oct signals by parallel detection of spectral bands
US20080097225 *Oct 19, 2007Apr 24, 2008The General Hospital CorporationApparatus and method for obtaining and providing imaging information associated with at least one portion of a sample, and effecting such portion(s)
US20080097709 *Dec 13, 2007Apr 24, 2008The General Hospital CorporationApparatus and method for rangings and noise reduction of low coherence interferometry lci and optical coherence tomography oct signals by parallel detection of spectral bands
US20080129981 *May 4, 2007Jun 5, 2008David D NolteMolecular interferometric imaging process and apparatus
US20080144899 *Nov 29, 2007Jun 19, 2008Manoj VarmaProcess for extracting periodic features from images by template matching
US20080170225 *Dec 12, 2007Jul 17, 2008The General Hospital CorporationApparatus and method for ranging and noise reduction of low coherence interferometry lci and optical coherence tomography oct signals by parallel detection of spectral bands
US20080175280 *Jan 17, 2008Jul 24, 2008The General Hospital CorporationWavelength tuning source based on a rotatable reflector
US20080181263 *Apr 11, 2008Jul 31, 2008The General Hospital CorporationProcess and apparatus for a wavelength tuning source
US20080206804 *Jan 17, 2008Aug 28, 2008The General Hospital CorporationArrangements and methods for multidimensional multiplexed luminescence imaging and diagnosis
US20080230605 *Nov 30, 2007Sep 25, 2008Brian WeichelProcess and apparatus for maintaining data integrity
US20080232410 *Mar 21, 2008Sep 25, 2008The General Hospital CorporationMethods, arrangements and apparatus for utilizing a wavelength-swept laser using angular scanning and dispersion procedures
US20080234567 *Mar 19, 2008Sep 25, 2008The General Hospital CorporationApparatus and method for providing a noninvasive diagnosis of internal bleeding
US20080234586 *Mar 19, 2008Sep 25, 2008The General Hospital CorporationSystem and method for providing noninvasive diagnosis of compartment syndrome using exemplary laser speckle imaging procedure
US20080262314 *Apr 17, 2008Oct 23, 2008The General Hospital CorporationApparatus and methods for measuring vibrations using spectrally-encoded endoscopy
US20080262359 *Mar 28, 2008Oct 23, 2008The General Hospital CorporationSystem and method providing intracoronary laser speckle imaging for the detection of vulnerable plaque
US20090003765 *Sep 5, 2008Jan 1, 2009The General Hospital CorporationImaging system and related techniques
US20090036782 *Jul 31, 2008Feb 5, 2009The General Hospital CorporationSystems and methods for providing beam scan patterns for high speed doppler optical frequency domain imaging
US20090059360 *Aug 29, 2008Mar 5, 2009The General Hospital CorporationSystem and method for self-interference fluorescence microscopy, and computer-accessible medium associated therewith
US20090073439 *Sep 15, 2008Mar 19, 2009The General Hospital CorporationApparatus, computer-accessible medium and method for measuring chemical and/or molecular compositions of coronary atherosclerotic plaques in anatomical structures
US20090122302 *Oct 30, 2008May 14, 2009The General Hospital CorporationSystem and method for cladding mode detection
US20090131801 *Oct 13, 2008May 21, 2009The General Hospital CorporationSystems and processes for optical imaging of luminal anatomic structures
US20090192358 *Jul 30, 2009The General Hospital CorporationSystems, processes and computer-accessible medium for providing hybrid flourescence and optical coherence tomography imaging
US20090225324 *Jan 20, 2009Sep 10, 2009The General Hospital CorporationApparatus for providing endoscopic high-speed optical coherence tomography
US20090263913 *May 15, 2009Oct 22, 2009Nolte David DDifferentially encoded biological analyzer planar array apparatus and methods
US20090323056 *Dec 31, 2009The General Hospital CorporationMethods, arrangements and systems for obtaining information associated with a sample using optical microscopy
US20100093106 *Sep 14, 2007Apr 15, 2010Fortebio, Inc.Amine-Reactive Biosensor
US20100094576 *Sep 30, 2009Apr 15, 2010The General Hospital CorporationApparatus and method for ranging and noise reduction of low coherence interferometry lci and optical coherence tomography oct signals by parallel detection of spectral bands
US20100110414 *May 7, 2009May 6, 2010The General Hospital CorporationSystem, method and computer-accessible medium for tracking vessel motion during three-dimensional coronary artery microscopy
US20100157309 *Jul 27, 2009Jun 24, 2010The General Hospital CorporationSpeckle reduction in optical coherence tomography by path length encoded angular compounding
US20100165335 *Jul 31, 2007Jul 1, 2010The General Hospital CorporationSystems and methods for receiving and/or analyzing information associated with electro-magnetic radiation
US20100207037 *Aug 19, 2010The General Hospital CorporationSystem, method and computer-accessible medium for providing wide-field superresolution microscopy
US20100238453 *May 28, 2010Sep 23, 2010Fortebio, Inc.Fiber-Optic Assay Apparatus Based On Phase-Shift Interferometry
US20100309477 *Jun 7, 2010Dec 9, 2010The General Hospital CorporationMethod and apparatus for performing optical imaging using frequency-domain interferometry
US20110046016 *Oct 31, 2010Feb 24, 2011Axela Inc.Disposable reaction vessel with integrated optical elements
US20110092823 *Jul 19, 2010Apr 21, 2011The General Hospital CorporationSystem and Method for Identifying Tissue Using Low-Coherence Interferometry
US20110137178 *Jun 9, 2011The General Hospital CorporationDevices and methods for imaging particular cells including eosinophils
US20110144504 *Jun 16, 2011The General Hospital CorporationMethod and apparatus for optical imaging via spectral encoding
US20110149296 *Oct 22, 2010Jun 23, 2011The General Hospital CorporationMethod and apparatus for optical imaging via spectral encoding
US20110201924 *Jul 28, 2010Aug 18, 2011The General Hospital CorporationMethod and Apparatus for Improving Image Clarity and Sensitivity in Optical Tomography Using Dynamic Feedback to Control Focal Properties and Coherence Gating
US20110218403 *Sep 8, 2011The General Hospital CorporationSystems, methods and computer-accessible medium which provide microscopic images of at least one anatomical structure at a particular resolution
US20110222563 *Sep 15, 2011The General Hospital CorporationWavelength tuning source based on a rotatable reflector
US20110224541 *Dec 8, 2010Sep 15, 2011The General Hospital CorporationMethods and arrangements for analysis, diagnosis, and treatment monitoring of vocal folds by optical coherence tomography
US20110237892 *Jul 14, 2009Sep 29, 2011The General Hospital CorporationApparatus and methods for color endoscopy
USRE43875Nov 25, 2008Dec 25, 2012The General Hospital CorporationSystem and method for optical coherence imaging
USRE44042Mar 5, 2013The General Hospital CorporationSystem and method for optical coherence imaging
USRE45512Sep 12, 2012May 12, 2015The General Hospital CorporationSystem and method for optical coherence imaging
EP1610116A2 *Jun 10, 2005Dec 28, 2005Samsung Electronics Co., Ltd.Microstructured substrate having patterned thin layer, array of microstructures comprising the thin layer and methods of producing the microstructured substrate and the array of microstructures
EP1856692A2 *Feb 1, 2006Nov 21, 2007Purdue Research FoundationMethod and apparatus for phase contrast quadrature interferometric detection of an immunoassay
EP2026060A1 *Nov 5, 2004Feb 18, 2009Fortebio, IncOptical detection apparatus based on phase-shift interferometry
WO2005062021A1 *Dec 22, 2004Jul 7, 2005Axela Biosensors Inc.Disposable reaction vessel with integrated optical elements
WO2006083911A2 *Feb 1, 2006Aug 10, 2006Purdue Research FoundationMethod and apparatus for phase contrast quadrature interferometric detection of an immunoassay
WO2006083911A3 *Feb 1, 2006Oct 11, 2007Purdue Research FoundationMethod and apparatus for phase contrast quadrature interferometric detection of an immunoassay
WO2006083915A1 *Feb 1, 2006Aug 10, 2006Purdue Research FoundationMultiplexed and differentially encoded biological analyzer planar array apparatus and methods
WO2007098365A1 *Feb 15, 2007Aug 30, 2007Purdue Research FoundationIn-line quadrature and anti-reflection enhanced phase quadrature interferometric detection
WO2013135933A1 *Mar 12, 2013Sep 19, 2013Universitat Politècnica De ValènciaMethod for the label-free identification of viruses and bacteria, using compact disc technology
Classifications
U.S. Classification422/82.05, 436/524
International ClassificationG01N21/45
Cooperative ClassificationG01N21/45, Y10T436/111666
European ClassificationG01N21/45
Legal Events
DateCodeEventDescription
Aug 6, 2002ASAssignment
Owner name: PURDUE RESEARCH FOUNDATION, INDIANA
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:NOLTE, DAVID D.;REGNIER, FRED E.;VARMA, MANOJ;REEL/FRAME:013151/0262;SIGNING DATES FROM 20020425 TO 20020726
May 25, 2004CCCertificate of correction
May 7, 2007FPAYFee payment
Year of fee payment: 4
Sep 12, 2011REMIMaintenance fee reminder mailed
Jan 4, 2012SULPSurcharge for late payment
Year of fee payment: 7
Jan 4, 2012FPAYFee payment
Year of fee payment: 8
Jul 27, 2015FPAYFee payment
Year of fee payment: 12